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Randall LM , Monk BJ , Moon J , Parker R , Al-Ghazi M , Wilczynski S , Fruehauf JP , Markman M , Burger RA
Prospective evaluation of an in vitro radiation resistance assay in locally advanced cancer of the uterine cervix: A Southwest Oncology Group Study
Gynecologic Oncology. 2010 Dec;119(3) :417-421
PMID: ISI:000284556800004   
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Abstract
Objectives. To investigate the feasibility of performing a fresh-tissue, in vitro radiation resistance assay (IVRRA) in a cooperative group setting and to assess the association of IVRRA results with clinical outcomes. Methods. Women with Stages IIB-IVA carcinoma of the uterine cervix without obvious para-aortic lymphadenopathy on imaging were eligible. Primary tumor biopsies were shipped to a central testing facility where agar-based cell suspensions were exposed to 300 cGy of RT +/- cisplatin and cultured for 5 days. H-3-thymidine incorporation was used to determine percent cell inhibition (PCI) of test specimen compared to that of the untreated control. Tumors were considered to exhibit extreme radiation resistance (ERR), intermediate radiation resistance (IRR) or low radiation resistance (LRR) based on a standard data set from 39 previously studied specimens. Standardized doses of external beam radiation and intracavitary brachytherapy, when feasible, in addition to platinum-based chemotherapy were mandated. Progression-free survival (PFS) was the primary endpoint. Clinical response and overall survival (OS) were secondary endpoints. Clinical investigators were blinded to assay data and vice versa. Results. Thirty-six patients were enrolled, but analysis was limited to 17 patients whose specimens were adequate for IVRRA. The median follow-up time among patients still alive at last contact was 40 months (range: 0-56 months). There was no association between IVRRA and response. In the Cox model, IRR/ERR tumors showed worse PFS [HR=11.2 (95% CI 1.3-96, p=0.03)] and worse OS [HR=11.7 (95% CI 1.4-99.6, p=0.03)] compared to LRR tumors when IVRRA was performed with RT alone, but there were no associations between IVRRA and PFS or OS when cisplatin was added to the IVRRA. Conclusions. IVRRA (RT alone) results correlated with PFS and OS in this prospective trial, but follow-up trials are indicated to address feasibility and to confirm results in an expanded cohort. If confirmed, IVRRA could potentially direct molecular identification of novel targeted therapeutic approaches which might counteract radiation resistance. (C) 2010 Elsevier Inc. All rights reserved.
Notes
Randall, Leslie M. Monk, Bradley J. Moon, James Parker, Ricardo Al-Ghazi, Muthana Wilczynski, Sharon Fruehauf, John P. Markman, Maurie Burger, Robert A. National Cancer Institute, DHHS [CA86780, CA22433, CA58723, CA37981, CA32102, CA38926]; Oncotech This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA86780, CA22433, CA58723, CA37981, CA32102, CA38926, and supported in part by Oncotech. 25 Academic press inc elsevier science; 525 b st, ste 1900, san diego, ca 92101-4495 usa 684no